BackgroundDiquat is a common environmental pollutant, which can cause oxidative stress in humans and animals. Diquat exposure cause growth retardation and intestinal damage. Therefore, this study was performed to investigate the effects of melatonin on diquat challenged piglets.ResultsThe result showed that dietary supplementation with 2 mg/ kg melatonin significantly increased the average daily gain (ADG), and feed conversion rate in piglets. Melatonin increased antioxidants capacity, and improves intestinal epithelial barrier function of duodenum and jejunum in piglets. Moreover, melatonin also regulates the expression of immune and antioxidant related genes. Furtherly, melatonin also alleviates diquat induced growth retardation, and anorexia in diquat‐challenged piglets. Moreover, melatonin also increased antioxidants capacity, and ameliorate diquat induced intestinal epithelial barrier injury. Melatonin regulated the expression of MnSOD in intestinal, and immune related genes.ConclusionIn conclusion, dietary supplementary with 2 mg/kg melatonin increased antioxidant capacity to ameliorate diquat‐induced oxidative stress, alleviates intestinal epithelial barrier injury, and increased growth performance in weaned piglets.This article is protected by copyright. All rights reserved.